Normal human embryonic stem cells are pluripotent stem cells that differentiate into the two-hundred different types of cells that make up the human body. Embryonal carcinoma is a human cancerous pluripotent stem cell derived from human germ cell tumors and is known as the malignant equivalent of normal embryonic stem cells. Both normal embryonic stem cells and embryonal carcinoma express pluripotent-associated antigens on the surface of their plasma membrane. It is known that at least some pluripotent-associated antigens are lost during differentiation and are not expressed or lowly expressed in normal cells and tissues.
It is known that many human cancers have an embryonic stem cell gene signature and re-express pluripotent and embryonic antigens not present or lowly present in normal differentiated cells. The Cellular Reprogramming theory of the origin of cancer states that the cause of cancer is due to a normal cell reprogramming and undergoing dedifferentiation backwards towards a primitive embryonic-like cancer cell with stem cell properties. It is believed these primitive embryonic-like cancer stem cells are the origin of cancer and are the drivers of disease progression, and disease resistant which almost universally occurs with conventional therapies. Furthermore, it is thought that therapeutic targeting and eliminating of these primitive embryonic-like cancer stem cells will result in meaningful and lasting cancer treatments.
Podocalyxin is a cell surface glycoprotein that is highly expressed on human embryonic stem cells and pluripotent cancer stem cells. The podocalyxin protein expressed on embryonic and pluripotent cells has additional carbohydrate groups (TRA-1-60 and TRA-1-81 which are herein referred to as TRA) attached to the podocalyxin protein. The TRA carbohydrate groups are embryonic and pluripotent specific and are not present on somatic or differentiated cells. The pluripotent and embryonic version of podocalyxin is call TRA-Podocalyxin. It is known that the embryonic and pluripotent form TRA-Podocalyxin is re-expressed in many types of cancer
Monoclonal antibodies can be produced that are specific and reactive to pluripotent antigens expressed on the surface of cancer cells and normal embryonic cells, but not on normal differentiated cells of the body. Furthermore, monoclonal antibodies can be produce that are reactive and have specific binding activity to TRA-Podocalyxin. These antibodies can be used as anti-cancer therapeutic agents for cancers which re-express embryonic and pluripotent antigens such as TRA-Podocalyxin during the onset and progression of the disease.
It is an object of the invention to develop a pluripotent- and an embryonic stem cell-specific antibody. In addition, it is an object of the invention to develop a TRA-Podocalyxin specific antibody. Further, it is an object to develop a therapeutic agent or composition that includes the antibody or a fragment thereof as an active ingredient. Furthermore, it is an object to introduce or administer the therapeutic agent or composition to a cancer patient to regress, reduce or eliminate cancer cells in the patient.